Predictive model for iris melanoma.

AimTo develop a predictive model for the diagnosis of iris melanoma. METHODS: Retrospective consecutive case series that included 100 cases of pathologically confirmed iris melanoma and 112 cases of Iris naevus, either pathological confirmation or documented stability of >1 year. Patient demographic data, features of clinical presentation, tumour characteristics and follow-up were collected. Iris melanoma with ciliary body extension was excluded. Lasso logistic regression with 10-fold cross-validation was used to select the tuning parameter. Discrimination was assessed with the area under the curve (AUC) and calibration by a plot. RESULTS: There was a significant asymmetry in the location of both nevi and melanoma with preference for inferior iris quadrants (83, 74%) and (79, 79%), respectively (p=0.50). Tumour seeding, glaucoma and hyphaema were present only in melanoma. The features that favoured the diagnosis of melanoma were size (increased height (OR 3.35); increased the largest basal diameter (OR 1.64)), pupillary distortion (ectropion uvea or corectopia (OR 2.55)), peripheral extension (angle or iris root involvement (OR 2.83)), secondary effects (pigment dispersion (OR 1.12)) and vascularity (OR 6.79). The optimism-corrected AUC was 0.865. The calibration plot indicated good calibration with most of the points falling near the identity line and the confidence band containing the identity line through most of the range of probabilities. CONCLUSIONS: The predictive model provides direct diagnostic prediction of the lesion being iris melanoma expressed as probability (%). Use of a prediction calculator (app) can enhance decision-making and patient counselling. Further refinements can be undertaken with additional datasets, forming the basis for automated diagnosis.

A PIGMENTED FUNDUS LESION WITH PSEUDOHYPOPYON AND SUBRETINAL FLUID RESEMBLING UNILATERAL RETINAL PIGMENT EPITHELIUM DYSGENESIS.

PURPOSE: To describe multimodal imaging findings in a patient with a rare, symptomatic fundus lesion arising from the retinal pigment epithelium. METHODS: Case report. RESULTS: A 36-year-old woman presented with photopsia in her left eye. Funduscopy revealed an 8-mm × 7-mm, dark brown lesion at the level of the retinal pigment epithelium inferior to the macula. The lesion had an irregular, cauliflower-like border and a light grey subretinal pseudohypopyon. On fundus autofluorescence, the lesion was markedly hypoautofluorescent with an irregular hyperautofluorescent margin. It was generally hyopofluorescent on fluorescein angiography and moderately hypofluorescent on indocyanine green angiography. Spectral-domain optical coherence tomography revealed a fine layer of subretinal fluid over the entire lesion, thinning of the outer retinal layers with loss of photoreceptors, and an irregular retinal pigment epithelium. Multiple drusen-like subretinal deposits were located along the lesion margin, and inferiorly, the pseudohypopyon appeared as a hyperreflective subretinal mass. During 3 years of follow-up, her symptoms remained unchanged and fundus photography showed minimal enlargement of the lesion. CONCLUSION: Multimodal imaging findings of a solitary pigmented retinal pigment epithelium lesion with pseudohypopyon and subretinal fluid are shown. The lesion may represent an atypical variant of unilateral retinal pigment epithelium dysgenesis.

Air versus Sulfur Hexafluoride Gas Tamponade for Small and Medium-Sized Macular Holes: A Randomized Noninferiority Trial.

PURPOSE: To investigate whether air tamponade is noninferior to sulfur hexafluoride (SF6) gas tamponade for small (≤ 250 µm) and medium-sized (> 250 µm and ≤ 400 µm) macular holes (MHs). DESIGN: Multicenter, randomized controlled, noninferiority trial. PARTICIPANTS: Patients aged ≥ 18 years undergoing surgery for primary MHs of ≤ 400 µm in diameter. METHODS: The patients in both groups underwent conventional pars plana vitrectomy with peeling of the internal limiting membrane. At the end of the surgery, the patients were randomized to receive either air or SF6 gas tamponades, stratified by MH size. Postoperatively, the patients followed a nonsupine positioning regimen for 3 days. MAIN OUTCOME MEASURES: The primary end point was the MH closure rate after a single surgery, confirmed by OCT after 2 to 8 weeks. The noninferiority margin was set at a 10-percentage-point difference in the closure rate. RESULTS: In total, 150 patients were included (75 in each group). In the intention-to-treat (ITT) analysis, 65 of 75 patients in the air group achieved primary closure. All 75 MHs in the SF6 group closed after a single surgery. Six patients were excluded from the per-protocol (PP) analysis. In the PP analysis, 63 of 70 patients in the air group and all 74 patients in the SF6 group achieved MH closure after a single surgery, resulting in closure rates of 90% (95% confidence interval [CI], 79.9%-95.5%) and 100% (95% CI, 93.9%-100%), respectively. For the difference in closure rates, the lower bound of a 2-sided 95% CI exceeded the noninferiority margin of 10% in both ITT and PP analyses. In the subgroups of small MHs, all 20 patients in the air group and all 28 patients in the SF6 group achieved primary closure. CONCLUSIONS: This prospective randomized controlled trial proved that air tamponade is inferior to SF6 tamponade for MHs of ≤ 400 µm in diameter.

Topography and clinical features of iris melanoma.

BACKGROUND: To characterise the topographical and clinical features of primary iris melanoma and to visualise the patterns of tumour extent in the iris. METHODS: Clinical characteristics of iris melanomas were analysed, and data on their size, shape, and location were converted into a database of two-dimensional iris charts by means of computer-drawing software. The geometric centre of each tumour was entered into corresponding sectors of the chart. The extent of the melanomas was computationally visualised by merging the iris drawings and displaying the number of overlapping tumours on colour-coded iris maps. RESULTS: Twenty-nine patients (18 females and 11 males) with a mean age of 52 years met the inclusion criteria. The mean largest tumour diameter was 6.1 mm (range, 1.8-11.0 mm). Five tumours (17%) involved the pupillary margin, 10 (34%) involved the iris root, and 10 (34%) involved both sites. The hemispheric location of the tumour centroid was superior in 3 eyes (11%) and inferior in 25 (89%) (p < 0.0001), and the distribution between the temporal and nasal hemispheres was 17 (61%) and 11 (39%), respectively (p = 0.26). In females, the iris melanomas were located more temporally (p  =  0.02) and had more often originated from a pre-existing naevus (p = 0.03), than in males. There was also shift towards more temporally located melanomas in younger patients. CONCLUSIONS: The lower temporal iris quadrant is the preferential area of melanoma occurrence and growth. Iris melanoma tends to be more temporally located in females, who compared with males also have a higher proportion of melanomas arising from a pre-existing naevus.

Vitrectomy-Assisted Biopsy: An in vitro Study on the Impact of Cut Rate and Probe Size.

PURPOSE: The aim of this study was to optimize the technique of performing vitrectomy-assisted biopsy of intraocular tumors by comparing the cytohistological findings in specimens obtained with different vitrectomy probes and cut rates. METHODS: Vitrectomy-assisted biopsies were taken from a fresh porcine liver. For each sampling, the vacuum level was 300 mm Hg. The following parameters were compared; cut rate (60, 600 and 6,000 cuts per minute [cpm]), probe type (standard and two-dimensional cutting [TDC]), and probe diameter (23-gauge and 25-gauge). The specimens were assessed by automated whole-slide imaging analysis and conventional light microscopy. RESULTS: Seventy-two biopsies were analyzed for the number of hepatocytes, total area of tissue fragments, and total stained area of each microscope slide. For all probe types, these parameters were significantly and positively correlated with the cut rate. TDC probes led to significantly higher scores than those of standard probes, independent of the cut rate. There were no significant differences in results when using 23-gauge or 25-gauge standard probes. Light microscopic examination demonstrated well-preserved cells sufficient for cytohistological analyses in all investigated cases. CONCLUSIONS: The higher the cut rate, the larger is the amount of aspirated cellular material. There were no significant differences between 23-gauge and 25-gauge biopsies. Cut rates up to 6,000 cpm did not adversely affect the cytohistological features of the samples.

Optical coherence tomography features and risk of macular hole formation in the fellow eye.

BACKGROUND: To investigate the risk of primary macular hole (MH) in the fellow eye, and to evaluate baseline characteristics and optical coherence tomography (OCT) features that precede MH formation in the fellow eye. METHODS: A retrospective review of 229 patients treated for primary MH at Stavanger University Hospital, Norway, from January 2008 through December 2018. The patients were categorised into two groups according to subsequent development of MH in the fellow eye. The OCT findings of the two groups were compared, and associated risk factors for MH formation assessed. RESULTS: Twenty cases of bilateral MH were identified. The overall bilateral disease risk was 8.8% (95% CI, 5.8-13.2%). Two patients were previously operated in the fellow eye, six patients presented with bilateral MH, and 12 patients subsequently developed MH in the fellow eye. The risk of subsequent MH development was 5.7% (95% CI, 3.3-9.8%). Although the extent of posterior vitreous detachment (PVD) tended to be more progressed in the bilateral group compared with the unilateral group, the difference was not statistically significant. In the bilateral group, 41.7% had outer retinal defects vs 6.6% in the unilateral group (p = 0.001), and 33.3% in the bilateral group had intraretinal pseudocysts vs 10.2% in the unilateral group (p = 0.036, not significant after multiple testing correction). CONCLUSION: Outer retinal defects and intraretinal pseudocysts are associated with an increased risk of MH formation in the fellow eye, and complete PVD indicates a decreased risk of MH formation.

STRUCTURAL PATHOLOGY AFTER RETINAL DETACHMENT: Multicolor Confocal Scanning Laser Ophthalmoscopy Versus Color Fundus Photography.

PURPOSE: To compare pathology detection using multicolor confocal scanning laser ophthalmoscopy with color fundus photography following macula-off rhegmatogenous retinal detachment. METHODS: Postsurgery multicolor confocal scanning laser ophthalmoscopy and color fundus photography images from 30 rhegmatogenous retinal detachment patients were examined by 10 masked graders. Imaging was performed with the Heidelberg Spectralis HRA and the digital retinal camera Basler acA2500-14gc GigE. Swept-source optical coherence tomography was used as verification modality. Detection rates of ellipsoid zone disruption, foveal ellipsoid zone rosette, outer retinal folds, intraretinal cysts, subretinal fluid layer, subretinal fluid blebs, retinal striae, and retinal detachment line were compared. Intermodality and intergrader agreement were estimated. RESULTS: Overall pathology detection was significantly higher for multicolor confocal scanning laser ophthalmoscopy multicolor confocal scanning laser ophthalmoscopy (adjusted odds ratio = 7.39; 95% confidence interval, 1.64-33.30; P = 0.009). The intermodality and intergrader agreement on overall pathology detection were moderate. The intermodality agreement was 0.49 (95% confidence interval, 0.48-0.51; P < 0.0001) (Gwet's AC1). Intergrader agreement was 0.53 (95% confidence interval, 0.52-0.54; P < 0.0001) for multicolor confocal scanning laser ophthalmoscopy and 0.58 (95% confidence interval, 0.57-0.59; P < 0.0001) (Fleiss kappa) for color fundus photography. CONCLUSION: Multicolor confocal scanning laser ophthalmoscopy imaging is superior to color fundus photography in detecting and delineating structural retinal abnormalities following rhegmatogenous retinal detachment and can be a helpful tool in the visualization of retinal remodeling processes in patients recovering from rhegmatogenous retinal detachment surgery.

Simultaneous bilateral aqueous misdirection following certolizumab therapy for rheumatoid arthritis.

Aqueous misdirection syndrome is a rare, incompletely understood, sight-threatening eye condition that is difficult to diagnose and treat. We present a case of simultaneous bilateral aqueous misdirection following the administration of certolizumab in a 41-year-old women with rheumatoid arthritis and no known risk factors. To our knowledge, aqueous misdirection has not previously been associated with the use of tumour necrosis factor-alpha inhibitors.

Cherenkov Luminescence Imaging for Assessment of Radioactive Plaque Position in Brachytherapy of Uveal Melanoma: An In Vivo Feasibility Study.

Purpose: To study the feasibility of using Cherenkov luminescence imaging (CLI) to evaluate and document ruthenium-106 plaque position during brachytherapy of uveal melanoma. Methods: Ruthenium-106 decays by emitting high-energy beta particles. When the electrons pass through the eye, Cherenkov radiation generates a faint light that can be captured by highly sensitive cameras. Patients undergoing ruthenium-106 plaque brachytherapy for posteriorly located choroidal melanoma were examined by CLI, which was performed in complete darkness with an electron multiplying charged-coupled device camera mounted on a fundus camera modified for long exposures. Results: Ten patients with tumors ranging from 5.8 to 13.0 mm in largest basal diameter and 2.0 to 4.6 mm in height were included. The plaques had an activity between 0.035 and 0.089 MBq/mm2 at the time of examination (1-4 days after implantation). CLI revealed the actual plaque position by displaying a circular area of light in the fundus corresponding with the plaque area. The Cherenkov light surrounded the tumor as a halo, which showed some asymmetry when the plaque was slightly displaced. The light intensity correlated positively with plaque activity and negatively with tumor pigmentation. Exposure times between 30 and 60 seconds were required to display the plaque position and delineate the tumor area. The long exposures made it difficult to maintain stable eye fixation and optimal image quality. Conclusions: CLI is a novel method to assess and document ruthenium-106 plaque position in brachytherapy for uveal melanoma. Translational Relevance: Ocular CLI may provide relevant radiation data during and after implantation of radioactive plaques, thus improving the accuracy of episcleral brachytherapy.

Drusenoid pigment epithelial detachment volume is associated with a decrease in best-corrected visual acuity and central retinal thickness: the Norwegian Pigment Epithelial Detachment Study (NORPED) report no. 1.

PURPOSE: To investigate the association of drusenoid pigment epithelial detachment (DPED) volume and change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) during the growth phase of large DPEDs. METHODS: Patients from an ongoing prospective observational study, the Norwegian Pigment Epithelial Detachment Study (NORPED), with 1 year of follow-up and DPEDs ≥1000 µm in diameter, examined with the Heidelberg Spectralis HRA-OCT were included. Patients with DPEDs in the regression phase were excluded. Multicolour, near-infrared reflectance, optical coherence tomography (OCT) and OCT angiography images were obtained every 6 months. Fluorescein angiography and indocyanine green angiography were performed at baseline and yearly to exclude choroidal neovascularization (CNV). RESULTS: Forty-four patients and 66 eyes were included. In the statistical model for BCVA, every 1.0 mm3 increase in DPED volume led to a decrease in BCVA of 4.0 ETDRS letters (95% CI, -7.0 to -1.0, p = 0.008). A decrease in BCVA was significantly associated with older patient age, the presence of acquired vitelliform lesions and subfoveal location of the DPEDs. In the model for CRT, every 1.0 mm3 increase in DPED volume led to a decrease in CRT of 26.7 µm (95% CI, -44.4 to -9.0, p = 0.003). Two eyes had progression of geographic atrophy and none developed CNV. CONCLUSION: The increasing volume of DPEDs during the growth phase is associated with a decrease in BCVA and CRT. The subfoveal location of DPEDs and the presence of acquired vitelliform lesions appear to be associated with a further reduction in BCVA.

Effect of Apraclonidine and Diclofenac on Early Changes in Intraocular Pressure After Selective Laser Trabeculoplasty.

PRéCIS:: Adjuvant diclofenac and apraclonidine eye drop given in conjunction with selective laser trabeculoplasty (SLT) do not significantly impact medium-term intraocular pressure (IOP) reduction compared with placebo, but apraclonidine can be used to blunt immediate postlaser pressure spikes. PURPOSE: There is limited high-grade evidence guiding the choice of eye drops given before and after SLT. The authors chose to measure IOP during the first 24 hours, at 1 week, 6 weeks, and 6 months after SLT, and compare the effect of apraclonidine before SLT and diclofenac after SLT, with placebo. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, patients with open-angle glaucoma or ocular hypertension referred for SLT were recruited between 2016 and 2018. Patients were randomized to receive either apraclonidine pre-SLT with placebo post-SLT, placebo pre-SLT with diclofenac post-SLT, or placebo before and after SLT. RESULTS: Sixty eyes from 35 patients were treated with 360-degree SLT. Twenty-four-hour IOP measurements with patient self-monitoring after SLT demonstrated a moderate IOP spike at 1 hour and 2 hours post-SLT in the placebo and diclofenac study arms (mean=+4.05±0.58 mm Hg and +4.47±0.73, respectively, P<0.001 vs. pre-SLT IOP), which was prevented by apraclonidine (mean=-2.41±0.88 mm Hg, P<0.0001 vs. other study arms post-SLT). There were no significant differences between the 3 arms of the study on the long-term IOP reduction achieved by SLT (6 wk: P=0.51, 6 mo: P=0.42). CONCLUSIONS: Neither the use of apraclonidine before SLT nor diclofenac after SLT significantly influenced the IOP reduction induced by SLT. Except for a slight and transient reduction in intraocular inflammation, there was no beneficial effect of diclofenac on early IOP changes or the degree of patient discomfort relative to placebo.

Nonsupine Positioning after Macular Hole Surgery: A Prospective Multicenter Study.

PURPOSE: To evaluate the postoperative closure rate of full-thickness macular holes (MHs) after nonsupine positioning, which means that the patients avoid upward gaze and a supine sleeping position, and to investigate the correlation between postoperative positioning compliance and closure rate. DESIGN: Prospective, multicenter study (ClinicalTrials.gov identifier, NCT02295943). PARTICIPANTS: Patients undergoing primary surgery for primary MH. METHODS: Patients underwent pars plana vitrectomy with internal limiting membrane peeling and sulfur hexafluoride gas tamponade followed by 3 to 5 days of nonsupine positioning. A positioning measuring device that recorded the time spent in the supine position was attached to patients' forehead after surgery for 24 hours. MAIN OUTCOME MEASURES: Anatomic closure rate of MH at 2 weeks or more after surgery and the time spent in supine position during the first 24 hours after surgery. RESULTS: A total of 205 participants were included, of whom 2 were lost to follow-up. Two hundred two of 203 MHs closed after a single operation, giving a closure rate of 99.5% (95% confidence interval, 97.3%-99.9%). The median time of supine positioning during the first 24 hours was 28 seconds (range, 0:00:00-01:52:28). Because of the very high closure rate, a correlation between positioning compliance and closure rate could not be established. CONCLUSIONS: Pars plana vitrectomy with internal limiting membrane peeling followed by a short-term nonsupine positioning accomplished a very high MH closure rate. Thus, face-down positioning was not necessary to achieve excellent closure rates in this study.

Treatment of large avascular retinal pigment epithelium detachments in age-related macular degeneration with aflibercept, photodynamic therapy, and triamcinolone acetonide.

PURPOSE: To evaluate the use of aflibercept, triamcinolone acetonide, and photodynamic therapy (PDT) in the treatment of avascular pigment epithelium detachments (aPEDs). PATIENTS AND METHODS: Patients with treatment-naïve aPEDs ≥1,500 µm in diameter were randomized to treatment or observation. Treatment consisted of 6 monthly intravitreal injections of aflibercept. If the aPED persisted, the patients were treated with half-fluence PDT in combination with intravitreal triamcinolone acetonide and aflibercept. The primary outcome was change of best-corrected visual acuity (BCVA) after 24 months of follow-up. Secondary outcomes were changes in pigment epithelium volume, height and diameter, central retinal thickness, and number of patients developing choroidal neovascularization or geographic atrophy (GA). RESULTS: Treatment and inclusion of patients were stopped after an interim analysis of 6-month data because 75% of the aPEDs were in different stages of GA. Nine patients with aPED were included in the study, of these one patient was excluded because of bilateral central serous chorioretinopathy. The remaining eight had drusenoid aPEDs. After 24 months of follow-up, estimated means of BCVA decreased by 4.2 and 20.8 letters in the treatment and observation group, respectively. This decrease over time was not significantly different between groups (P=0.140, 95% CI -5.3, 38.6). Estimated means of PED volume, height, diameter, and central retinal thickness were not significantly different between groups. Choroidal neovascularization and retinal pigment epithelium tear developed in one patient in the treatment group. One patient in the treatment group and two patients in the observation group progressed to complete retinal pigment epithelium and outer retinal atrophy. A decrease in PED volume was associated with the development of complete retinal pigment epithelium and outer retinal atrophy (P=0.029). CONCLUSION: This small trial indicates that multitargeted, primarily antiangiogenic therapy does not favorably alter the natural course of drusenoid aPEDs.

Circumscribed choroidal haemangioma: clinical and topographical features.

AIMS: To characterise the clinical and topographical features of circumscribed choroidal haemangioma (CCH) and to visualise the patterns of tumour extent in the ocular fundus. METHODS: Data on the size, shape and location of 113 CCH were converted into a database of two-dimensional retinal charts by means of computer drawing software. The extent of the tumours was visualised by merging the charts and displaying the number of overlapping tumours on colour-coded maps. RESULTS: The mean largest tumour diameter was 7.2 mm (range, 2.5-11.0 mm), mean tumour height was 2.4 mm (range, 0.7-4.6 mm) and mean diameter/height ratio was 3.2 (range, 2.1-6.0). The mean distance from the posterior tumour margin to the foveola and optic disc margin was 1.7 mm (range, 0-15 mm) and 2.4 mm (range, 0-11 mm), respectively. The hemispheric location of the tumour centroid was temporal in 75 eyes (66%) and nasal in 38 (34%) (p=0.0005) and the distribution between the superior and inferior hemispheres was 68 (60%) and 45 (40%), respectively (p=0.03). The presence of subretinal fluid (SRF) was significantly associated with young age at diagnosis (p=0.0002), low tumour diameter/height ratio (p=0.0004), nasal hemisphere location (p=0.006) and close proximity to the optic disc (p=0.004). CONCLUSIONS: The superotemporal quadrant close to the macula is the most frequent location of CCH. The tumours are generally characterised by a diameter/height ratio of >2. Tumours in young patients, with marked elevation, in nasal hemisphere and in proximity to the optic disc are associated with SRF exudation.

Diabetic retinopathy in type 1 diabetes patients in Western Norway.

PURPOSE: To describe the prevalence of diabetic retinopathy (DR), associated risk factors and health-related quality of life (HRQoL) in a population-based cohort of patients with type 1 diabetes mellitus (DM1). METHODS: All patients underwent a general and ophthalmic examination including seven-field stereo fundus photography for grading of DR and diabetic macular oedema (DMO). Kaplan-Meier survival analyses were performed to evaluate disease progression in relation to diabetes duration, age and year of diabetes onset. HRQoL and its association with DR were assessed by the Medical Outcomes Study Short Form 36 (SF-36) questionnaire. RESULTS: A total of 237 DM1 patients were included. Mean age at inclusion was 34 years (range, 4-75 years), and mean diabetes duration was 19 years (range, 5 months-63 years). A total of 145 patients (61%) had DR. Sixty-two patients (26%) had mild, 39 (16%) moderate and 13 (5%) severe nonproliferative DR, while 31 (13%) had proliferative DR. The prevalence of DMO was 8%. The most important risk factors predicting severity of DR were diabetes duration (p < 0.0001) and HbA1c level (p < 0.0001). Neuropathy (p = 0.006), nephropathy (p = 0.004) and male gender (p = 0.02) were also significant predictors of DR. Compared to normative SF-36 data, there was a linear trend of decreasing HRQoL with increasing severity of DR that was statistically significant for the four physical dimension scores. CONCLUSION: The prevalence of DR in DM1 was largely within the range of previous reports. Diabetes duration, HbA1c level, neuropathy, nephropathy and male gender were all significant predictors of DR severity. The patients with more severe DR had lower HRQoL.